SH2B adapter protein 3 (SH2B3)
The protein contains 575 amino acids for an estimated molecular weight of 63225 Da.
Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Blood coagulation
Cell differentiation
Cellular response to chemokine
Cellular response to interleukin-3
Cytokine-mediated signaling pathway
Embryonic hemopoiesis
Erythrocyte development
Intracellular signal transduction
Megakaryocyte development
Monocyte homeostasis
Negative regulation of cell population proliferation
Negative regulation of chemokine-mediated signaling pathway
Negative regulation of Kit signaling pathway
Negative regulation of MAP kinase activity
Negative regulation of platelet aggregation
Negative regulation of protein kinase B signaling
Negative regulation of receptor signaling pathway via JAK-STAT
Negative regulation of response to cytokine stimulus
Negative regulation of tyrosine phosphorylation of STAT protein
Neutrophil homeostasis
Thrombopoietin-mediated signaling pathway
Molecular Function
Obsolete SH3/SH2 adaptor activity
Obsolete signal transducer activity
Phosphate ion binding
Protein tyrosine kinase binding
Signaling adaptor activity
Signaling receptor complex adaptor activity
Stem cell factor receptor binding
Transmembrane receptor protein tyrosine kinase adaptor activity
The reference OMIM entry for this protein is 222100
Diabetes mellitus, insulin-dependent; iddm
Diabetes mellitus, type i
Juvenile-onset diabetes; jod diabetes mellitus, insulin-dependent, 1, included; iddm1, included
Insulin-dependent diabetes mellitus 1, included
DESCRIPTION
The type of diabetes mellitus called IDDM is a disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. It is a genetically heterogeneous autoimmune disease affecting about 0.3% of Caucasian populations (Todd, 1990). Genetic studies of IDDM have focused on the identification of loci associated with increased susceptibility to this multifactorial phenotype. The classical phenotype of diabetes mellitus is polydipsia, polyphagia, and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.CLINICAL FEATURES
The term diabetes mellitus is not precisely defined and the lack of a consensus on diagnostic criteria has made its genetic analysis difficult. Diabetes mellitus is classified clinically into 2 major forms of the primary illness, insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM; 125853), and secondary forms related to gestation or medical disorders. Appearance of the IDDM phenotype is thought to require a predisposing genetic background and interaction with other environmental factors. Rotter and Rimoin (1978) hypothesized that there are at least 2 forms of IDDM: a B8 (DR3)-associated form characterized by pancreatic autoimmunity, and a B15-associated form characterized by antibody response to exogenous insulin. Interestingly, the DR3 and DR4 alleles seem to have a synergistic effect on the predisposition to IDDM based on the greatly increased risk observed in persons having both the B8 and B15 antigens (Svejgaard and Ryder, 1977). Rotter and Rimoin (1979) hypothesized a combined form. Tolins and Raij (1988) cited clinical and experimental evidence to support the idea that those IDDM patients in whom diabetic nephropathy (see 603933) eventually develops may have a genetic predisposition to essential hypertension. Gambelunghe et al. (2001) noted heterogeneity of the clinical and immunologic features of IDDM in relation to age at clinical onset. Childhood IDDM is characterized by an abrupt onset and ketosis and is associated with HLA-DRB1*04-DQA1*0301-DQB1*0302 and a high frequency of insulin and IA-2 autoantibodies. On the other hand, the so-called latent autoimmune diabetes of the adult (LADA) is a slowly progressive form of adult-onset autoimmune diabetes that is noninsulin-dependent at the time of clinical diagnosis and is characterized by the presence of glutamic acid decarboxylase-65 (GAD65: 138275) autoantibodies and/or islet cell antibodies.BIOCHEMICAL FEATURES
Nepom et al. (1987) studied the mechanism of the exaggerated susceptibility to IDDM in DR3/DR4 heterozygotes, and concluded that its basis is the formation of hybrid molecules of the closely linked DQ-alpha (HLA-DQA1; 146880) and -beta (HLA-DQB1; 604305) chains. The DR-alpha molecules are not polymorphic, and mixed DR alpha-beta dimers would not result in novel HLA molecules. On the other hand, both the alpha and beta chains of DQ are polymorphic, and a DQ alpha-beta dimer composed of transcomplementing chains would be unique to a heterozygous individual and not expressed in either parent. In the mouse, such transcomplementation has been demonstrated structurally, and epitopes newly formed in the resulting hybrid molecules allow for an altered functional immune response different f ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for SH2B3
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 222100 was added.